Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories.

Epidemiological and clinical characteristics of vaccinated COVID-19 patients: A meta-analysis and systematic review.

OBJECTIVE: With the global epidemic of coronavirus disease 2019 (COVID-19), vaccination rates are increasing globally. This study evaluated the relevant clinical manifestations of vaccinated COVID-19 patients. METHODS: We searched carefully in 11 databases such as PubMed, Embase, Scopus, Cochrane Library, Web of Science, Ovid, China National Knowledge Infrastructure Database, Wan Fang Data, Sinomed, VIP Database, and Reading Showing Database up to 26 March 2022. To search for articles that have described the characteristics of vaccinated patients including epidemiological and clinical symptoms. Statistical analysis of the extracted data using STATA 14.0. RESULTS: A total of 58 articles and 263,708 laboratory-confirmed COVID-19 patients were included. Most of the patients in the vaccinated group had more asymptomatic infection and fewer severe illnesses. There were significant differences in ethnicity, and strain infected with COVID-19, and comorbidities (hyperlipidemia, diabetes, obesity, kidney disease, immunocompromised, cardiovascular disease, and tumor) and symptoms (fever, cough, gastrointestinal symptoms, neurological symptoms, and dysgeusia/anosmia) between vaccinated group and unvaccinated group. Oxygen support, use of steroid, days in hospital, hospital treatment, ICU treatment, death, and poor prognosis were also significantly different. CONCLUSION: Compared with the vaccinated group, patients in the unvaccinated group had a more severe clinical manifestations. Vaccines are also protective for infected people.

Bibliometric analysis of traditional Chinese medicine for smoking cessation.

INTRODUCTION: Smoking cessation is an efficient approach to reducing disease burden. Traditional Chinese Medicine (TCM) therapies such as acupuncture, acupressure, and herbal drugs are often used to help quit smoking. However, there is a lack of overarching bibliometric analysis of the clinical research on smoking cessation focusing on TCM. The aim of our study is to explore the current patterns and trends of TCM therapy for smoking cessation through bibliometric methods with visual presentation. METHODS: This study is an assessment of academic publications retrieved from the Scopus database on smoking cessation using TCM therapy published in the period 2005-2021. Sankey diagram, word-cloud, network analysis, thematic maps, tree-maps, and the collaborative work of authors, institutions and countries, were used to identify research trends on TCM therapy for smoking cessation. The total cited index and H-index (for journals, authors, countries, organizations) were used to identify the trends of worldwide development by R Package and Excel 2016. RESULTS: There was an upward trend, with some fluctuations, of 1908 articles from 2005 to 2021. The most productive country was China. The top institution in this field was Beijing University. The dominant author that contributed to TCM therapy for smoking cessation was Wang Y, who has the highest H-Index. The most productive cited journals were Evidence-Based Complementary and Alternative Medicines and the Chinese Journal of Clinical Rehabilitation. Liu L, (2011, STROKE) had the highest centrality. The keywords 'acupuncture', 'traditional Chinese medicine', 'colitis', 'hypertension', 'chronic obstructive pulmonary disease', 'risk factors' and 'alternative medicine' ranked highest in frequency. The diseases of healthy people concerned mainly cardiovascular, cancer, diabetes, hypertension and pregnancy. The diseases of the patients concerned mainly cancer, diabetes, hematopathy, stroke, cardiovascular, diabetes, lung disease, and hypertension. Treatment methods were mainly traditional Chinese medicine and acupuncture. The research methods mainly included randomized controlled trials that were multi-center and double-blind. CONCLUSIONS: A substantial number of articles on TCM therapy for smoking cessation, mainly focusing on TCM and acupuncture were identified. It is worth noting that research that focused on TCM therapy for smoking cessation also was related to COVID-19.

Frailty is an independent determinant of COVID-19 vaccine hesitancy in the elderly: a cross-sectional study.

COVID-19 vaccines have become an important hope for slowing down or stopping the pandemic. As the population ages, older adults will comprise a greater proportion of the vaccinated population. We aimed to assess influencing factors of COVID-19 vaccine hesitancy in older adults. For this aim, We conducted a cross-sectional study on a questionnaire survey of the elderly over 65 years living in the community of Haikou City from August 1st to September 30th, 2021. Univariate and multivariate Logistic regression analyses were performed to identify factors related to vaccine hesitancy. We analyzed completed questionnaires from 225 respondents (42.2% women, mean age 73.4±6.2 years). There were 99 people in the vaccine hesitation group and 126 people in the vaccine acceptance group, the incidence of vaccine hesitation in the elderly population is about44%（99/225）. The incidence of frailty in the vaccine hesitation group was much higher than that in the vaccine trust group (62.63 vs. 30.95%, P＜0.001). The risk factors of vaccine hesitancy in the elderly aged 70-75years and over 75 years were 2.987 times and 3.587 times higher than that in the population aged 65-70 years (OR=2.987,95%CI: 1.424-6.265, P＜0.001; OR=3.587,95% CI:1.804-7.131, P＜0.001). Frailty is also an independent risk factor of vaccine hesitancy in the elderly population (OR=2.624,95%CI: 1.447-4.757, P＜0.001). Then the vaccination rate of the COVID-19 vaccine is far from reaching the requirements of herd immunity, and more flexible and comprehensive efforts are needed to increase the vaccination willingness of the frail elderly.

Case report on cured COVID-19 patients with viral nucleic acid test positive in fecal specimens in Chongqing, China

The outbreak of the novel coronavirus in China (2019-nCoV) has spread to all 31 provinces in China and more than 24 countries in the world. The cure criterion was based on the negative results with respiratory specimens in real-time reverse transcription polymerise chain reaction (RT-PCR) assays with an interval of 24 hrs. This report describes the controversial viral nucleic acid test in 27 cases after hospitalization for medical treatment for various periods. Of 27 cases, 6 cases showed positive results for fecal specimen, and 2 cases showed negative results with respiratory secretion but positive with fecal specimen. In summary, the consistence of results of nucleic acid test with different type of specimens from patients infected with 2019-nCoV varied, deeper research is needed to reveal the criteria of nucleic acid detection during different stages of the 2019-nCoV infection.

RASCL: Rapid Assessment Of SARS-CoV-2 Clades Through Molecular Sequence Analysis (preprint)

An important component of efforts to manage the ongoing COVID19 pandemic is the Rapid Assessment of how natural selection contributes to the emergence and proliferation of potentially dangerous SARS-CoV-2 lineages and CLades (RASCL). The RASCL pipeline enables continuous comparative phylogenetics-based selection analyses of rapidly growing clade-focused genome surveillance datasets, such as those produced following the initial detection of potentially dangerous variants. From such datasets RASCL automatically generates down-sampled codon alignments of individual genes/ORFs containing contextualizing background reference sequences, analyzes these with a battery of selection tests, and outputs results as both machine readable JSON files, and interactive notebook-based visualizations.

Stepwise evolution and exceptional conservation of ORF1a/b overlap in coronaviruses (preprint)

The programmed frameshift element (PFE) rerouting translation from ORF1a to ORF1b is essential for propagation of coronaviruses. A combination of genomic features that make up PFE--the overlap between the two reading frames, a slippery sequence, as well as an ensemble of complex secondary structure elements--puts severe constraints on this region as most possible nucleotide substitution may disrupt one or more of these elements. The vast amount of SARS-CoV-2 sequencing data generated within the past year provides an opportunity to assess evolutionary dynamics of PFE in great detail. Here we performed a comparative analysis of all available coronaviral genomic data available to date. We show that the overlap between ORF1a and b evolved as a set of discrete 7, 16, 22, 25, and 31 nucleotide stretches with a well defined phylogenetic specificity. We further examined sequencing data from over 350,000 complete genomes and 55,000 raw read datasets to demonstrate exceptional conservation of the PFE region.

Therapeutic effects and safety of oral Chinese patent medicine for COVID-19: A rapid systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Chinese patent medicine (CPM) is an indispensable part of traditional Chinese medicine. Coronavirus Disease 2019 (COVID-19) manifests is an acute respiratory infectious disease. This systematic review aimed to evaluate the therapeutic effects and safety of oral CPM for COVID-19. METHODS: We included randomized controlled trials (RCTs) that tested oral CPM for the treatment of COVID-19 identified from publications in CNKI, Wanfang, VIP, Web of Science, SinoMed, PubMed, Embase, BioRxiv, MedRxiv and arXiv before November 2nd, 2020. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool. RESULTS: Seven RCTs including 1079 participants were identified. The overall bias was assessed as "-high risk of bias" for all included trials. Oral CPM investigated were: Lianhua Qingwen capsule/granules (LHQW), Jinhua Qinggan granules (JHQG), Huoxiang Zhengqi dripping pills (HXZQ), Toujie Quwen granules (TJQW) and Lianhua Qingke granules (LHQK). Compared with conventional western therapy alone for people with COVID-19: regarding the main outcomes, the results showed that oral CPM combined with conventional western therapy improved cure rate (RR = 1.20, 95 % CI 1.04-1.38, involving LHQW and TJQW), reduced aggravation rate (RR = 0.50, 95 % CI 0.29 - 0.85, involving LHQW, JHQG, LHQK and TJQW); with regard to additional outcomes, the results showed that add-on oral CPM shortened the duration of fever, cough and fatigue, improved the recovery rate of cough and fatigue, and increased the improvement and recovery rate of chest CT manifestations. There were some differences in therapeutic effects among various CPMs for the same COVID-19 outcome. The use of TJQW and LHQG appeared not to increase the risk of adverse events, but JHQG may cause mild diarrhea. CONCLUSION: Low-certainty or very low-certainty evidence demonstrated that oral CPM may have add-on potential therapeutic effects for patients with non-serious COVID-19. These findings need to be further confirmed by well-designed clinical trials with adequate sample sizes.

Observed decreases in on-road CO2 concentrations in Beijing during COVID-19 restrictions

To prevent the spread of the COVID-19 epidemic, restrictions such as “lockdowns” were conducted globally, which led to a significant reduction in fossil fuel emissions, especially in urban areas. However, CO2 concentrations in urban areas are affected by many factors, such as weather, biological sinks and background CO2 fluctuations. Thus, it is difficult to directly observe the CO2 reductions from sparse ground observations. Here, we focus on urban ground transportation emissions, which were dramatically affected by the restrictions, to determine the reduction signals. We conducted six series of on-road CO2 observations in Beijing using mobile platforms before (BC), during (DC) and after (AC) the implementation of COVID-19 restrictions. To reduce the impacts of weather conditions and background fluctuations, we analyze vehicle trips with the most similar weather conditions possible and calculated the enhancement metric, which is the difference between the on-road CO2 concentration and the “urban background” CO2 concentration measured at the tower of the Institute of Atmospheric Physics (IAP), Chinese Academy of Sciences. The results showed that the DC CO2 enhancement was decreased by 41 (±1.3) parts per million (ppm) and 26 (±6.2) ppm compared to those for the BC and AC trips, respectively. Detailed analysis showed that, during COVID-19 restrictions, there was no difference between weekdays and weekends during working hours (09:00–17:00 local standard time;LST). The enhancements during rush hours (07:00–09:00 and 17:00–20:00 LST) were almost twice those during working hours, indicating that emissions during rush hours were much higher. For DC and BC, the enhancement reductions during rush hours were much larger than those during working hours. Our findings showed a clear CO2 concentration decrease during COVID-19 restrictions, which is consistent with the CO2 emissions reductions due to the pandemic. The enhancement method used in this study is an effective method to reduce the impacts of weather and background fluctuations. Low-cost sensors, which are inexpensive and convenient, could play an important role in further on-road and other urban observations.

Clinical features and potential mechanism of coronavirus disease 2019-associated liver injury.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has posed a serious threat to global public health security. With the increase in the number of confirmed cases globally, the World Health Organization has declared the outbreak of COVID-19 an international public health emergency. Despite atypical pneumonia as the primary symptom, liver dysfunction has also been observed in many clinical cases and is associated with the mortality risk in patients with COVID-19, like severe acute respiratory syndrome and Middle East respiratory syndrome. Here we will provide a schematic overview of the clinical characteristics and the possible mechanisms of liver injury caused by severe acute respiratory syndrome coronavirus 2 infection, which may provide help for optimizing the management of liver injury and reducing mortality in COVID-19 patients.

A CRISPR-Cas12a-based specific enhancer for more sensitive detection of SARS-CoV-2 infection.

BACKGROUND: Real-time reverse transcription-PCR (rRT-PCR) has been the most effective and widely implemented diagnostic technology since the beginning of the COVID-19 pandemic. However, fuzzy rRT-PCR readouts with high Ct values are frequently encountered, resulting in uncertainty in diagnosis. METHODS: A Specific Enhancer for PCR-amplified Nucleic Acid (SENA) was developed based on the Cas12a trans-cleavage activity, which is specifically triggered by the rRT-PCR amplicons of the SARS-CoV-2 Orf1ab (O) and N fragments. SENA was first characterized to determine its sensitivity and specificity, using a systematic titration experiment with pure SARS-CoV-2 RNA standards, and was then verified in several hospitals, employing a couple of commercial rRT-PCR kits and testing various clinical specimens under different scenarios. FINDINGS: The ratio (10 min/5 min) of fluorescence change (FC) with mixed SENA reaction (mix-FCratio) was defined for quantitative analysis of target O and N genes, and the Limit of Detection (LoD) of mix-FCratio with 95% confidence interval was 1.2≤1.6≤2.1. Totally, 295 clinical specimens were analyzed, among which 21 uncertain rRT-PCR cases as well as 4 false negative and 2 false positive samples were characterized by SENA and further verified by next-generation sequencing (NGS). The cut-off values for mix-FCratio were determined as 1.145 for positive and 1.068 for negative. INTERPRETATION: SENA increases both the sensitivity and the specificity of rRT-PCR, solving the uncertainty problem in COVID-19 diagnosis and thus providing a simple and low-cost companion diagnosis for combating the pandemic. FUNDING: Detailed funding information is available at the end of the manuscript.

The psychological impact of the COVID-19 epidemic on college students in China.

A COVID-19 epidemic has been spreading in China and other parts of the world since December 2019. The epidemic has brought not only the risk of death from infection but also unbearable psychological pressure. We sampled college students from Changzhi medical college by using cluster sampling. They responded to a questionnaire packet that included the 7-item Generalized Anxiety Disorder Scale (GAD-7) and those inquiring the participants' basic information. We received 7,143 responses. Results indicated that 0.9% of the respondents were experiencing severe anxiety, 2.7% moderate anxiety, and 21.3% mild anxiety. Moreover, living in urban areas (OR = 0.810, 95% CI = 0.709 - 0.925), family income stability (OR = 0.726, 95% CI = 0.645 - 0.817) and living with parents (OR = 0.752, 95% CI = 0.596 - 0.950) were protective factors against anxiety. Moreover, having relatives or acquaintances infected with COVID-19 was a risk factor for increasing the anxiety of college students (OR = 3.007, 95% CI = 2.377 - 3.804). Results of correlation analysis indicated that economic effects, and effects on daily life, as well as delays in academic activities, were positively associated with anxiety symptoms (P < .001). However, social support was negatively correlated with the level of anxiety (P < .001). It is suggested that the mental health of college students should be monitored during epidemics.